The proposed epidemiologic study of a cohort of 137,223 adults who underwent multiphasic health checkups (MHC) at Kaiser Permanente Medical Care Program in San Francisco and Oakland, California, will examine the relationship of low blood total cholesterol (TC) to health outcomes. It is expected to confirm relations between TC and atherosclerotic causes of death (positive) and between TC and nonatherosclerotic causes of death (inverse) recently reported by a consortium of 19 cohort studies. It will be the first to study the relations of TC to many of the corresponding causes of morbidity. Several diseases are of specific interest because of observed inverse associations with TC:hemorrhagic stroke; lung, hematopoietic, lymphatic and liver cancers; traumatic death, including suicide; chronic obstructive pulmonary disease and other respiratory diseases; hepatitis, liver cirrhosis and other digestive diseases; demyelinating diseases; and infections. Those self-reporting pre-existing diseases at an MHC examination will be excluded from disease-specific analysis, and there is extensive self-report alcohol intake information for investigation. Because the database is so large, highly specific diseases and hypotheses can be studied. Using life table methods, the differential time course of hazard by TC category will be examined, to see whether hazard lessens as time passes. This study will ask whether there are diseases for which TC associations are weak for morbidity, but play a stronger role in terminal phases of life. Since many people have repeat multiphasic exams, it will shed light on the time course of TC during disease, and on which diseases result in a lowered TC early in their natural history. This research will study gender, age and cigarette smoking interactions, and will help to delineate the nature of the relationships of low TC with nonatherosclerotic diseases: the extent to which they are due to confounding by such factors as excessive alcohol intake and pre-existing morbidity, and the extent to which plausible biological mechanisms may be operating. The proposed study aiming to clarify observed associations is particularly relevant because of current public health policy directed at dietary modifications that reduce TC levels in the entire population. We need to know the likely effect of this program in those with low TC at the outset.